tbuckley/cabot-search huggingface dataset:
Outcomes of pancreatic malignancy in octogenarians: A single tertiary center experience.
Authors: Mohammed Al-Jumayli, Juan Pablo Negrete Najar, Marina Sehovic, Maria Grazia Rodriquenz, Christine Sam, Cassandra Vonnes, Antonino Carmelo Tralongo, Martine Extermann
Journal: Journal of Clinical Oncology (2023)

e24008 Background: Pancreatic adenocarcinoma (PC) is generally diagnosed at a late stage, with a dismal prognosis. Patients aged 75-84 years constitute 28% of all patients. Surgery is the only way to cure, however, some surgeons have been hesitant to offer surgery to patients with advanced age due to lack of evidence available about the effectiveness and safety of treatments for this age group. Deficits accumulation frailty indices (FI) utilize readily available clinical data and easily obtained patient-reported information to predict hospitalization and mortality of older individuals. The goal of this large sample study is to profile octogenarians with PC. Methods: From 2015-2017, 440 patients over the age of 70 with biopsy confirmed PC were retrospectively reviewed. Among those, the outcomes of 129 (29.3%) pts older than 80 years of age were evaluated including patient’s characteristics, local control, systemic therapy, comprehensive geriatric assessment domains, specific geriatric outcomes and survival duration. Results: Median patients' age was 83 years (range 83-91) and 61(47.4%) were female. Patients with ECOG 0-1 at diagnosis were 109 pts (84.4%). Based on the FI, 28 patients (21.7%) were fit, while 79 (61.2%) were prefrail and 22 patients (17.1%) were frail. 33 patients (25.5%) presented as stage IV disease and 96(74.5%) as locally advanced PC. 46 patients (35.6%) had elective surgical resection. 53 patients (41.1%) received chemotherapy, 14 (10.8%) neoadjuvant, 17(20.9%) adjuvant and 12 (17.1%) palliative therapy. Among patients who had surgery, 10 (21.7%) had grade ≥3 adverse events and 6 (13%) had unplanned hospitalization. Median overall survival of resectable patients was 25.3 months. There was no statistically significant difference in survival after surgery in patients older than 80 years of age compared to younger than 80. Results of the multiple linear regression indicated that there was a moderate collective significant effect between the frailty index, ECOG, surgery, WT loss, albumin level, Cr clearance, Hb, and survival, (F(3,120) = 22, p &lt; .001, R = 0.35, R = 0.34). Frailty index (p = .027), ECOG (p &lt; .001) and surgery (p = .009) were significant individual predictors of the outcomes. Conclusions: Among older adult, Fit octogenarians experienced similar rate of mortality as patients younger than 80years old after elective pancreatic cancer surgery. Specific factors may also affect the outcome of surgery for older adults with cancer. These should be considered when assessing patients’ health and selecting them for surgery. A thorough preoperative evaluation can help ensure a better postoperative outcome.
Effect of SARS-CoV-2 mRNA vaccine booster in serologically negative patients with thymic epithelial tumors.
Authors: Erica Pietroluongo, Pietro De Placido, Rocco Morra, Roberto Buonaiuto, Margherita Tafuro, Alessandra Longobardi, Aldo Caltavituro, Marianna Tortora, Antonella Lucia Marretta, Vitoantonio Del Deo, Anna Maria Malfitano, Monica Gelzo, Bruno Daniele, Margaret Ottaviano, Pietro Formisano, Giuseppe Castaldo, Bianca Maria Veneziani, Giovannella Palmieri, Sabino De Placido, Mario Giuliano
Journal: Journal of Clinical Oncology (2023)

e20651 Background: Thymic epithelial tumors (TETs) are rare malignancies associated with humoral and cell-mediated immunity dysregulations. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. We have previously shown an impaired seroconversion after 1 st and 2 nd anti-SARS-CoV-2 vaccine doses in TETs patients. The aim of this study was to evaluate the seroconversion rate after the third vaccine dose (booster) in TET patients who remained serologically negative after full vaccination. Methods: Starting from November 2021 to March 2022, consecutive TET patients found to be serologically negative after two SARS-Cov-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech) doses were enrolled. SARS-CoV-2 spike-binding IgG antibody serological levels were centrally analyzed by chemiluminescent immunoassay (CLIA) at two different time-points: T0 and T1 (before and one month after booster, respectively). Cut-off for Ab titers positivity was &gt; 25 AU/mL. Results: Among the 23 enrolled patients, 10 (43.5%) were female and 13 (56.5%) males; 6 (26%) pts had thymic carcinoma and 17 (74%) had thymoma. Autoimmune disorders were detected in 20 patients (86.9%), of whom 3 (15%) suffered from Myasthenia Gravis, 8 (40%) from Good’s Syndrome, 7 (35%) from both diseases, and 2 (10%) from other autoimmune disorders. By the time of booster administration 2 pts were lost to follow up, 2 pts died, 5 pts suffered from SARS-CoV-2 infection and seroconverted. Of the remaining 14 pts, only 7 (50%) achieved seroconversion. Among these patients, 2 had active cancer disease, whereas the remaining were disease-free. On the other hand, among the 7 patients who did not achieve seroconversion after booster, 6 had active cancer disease. Moreover, 6 of these patients suffered from Good’s Syndrome. Conclusions: Our results suggest that the anti-SARS-CoV-2 third dose could contribute to improved seroconversion of TET patients who did respond to the first two doses. It remains to be investigated why half of the patients are still not achieving seroconversion after the booster and whether this is determined by the presence of active disease or by alterations in humoral and/or cell-mediated immune response. These data may have important clinical implications because they could help to better identify fragile patients who could benefit from improved vaccine protocols or from alternative prophylaxis strategies, such as the use of monoclonal antibodies.
Impact of genomic alterations measured in circulating tumor DNA (ctDNA) on clinical response to telisotuzumab vedotin treatment in patients with non-small cell lung cancer (NSCLC).
Authors: D. Ross Camidge, Shobhit Baijal, Athanasios Vasilopoulos, Christine Ratajczak, Jim Looman, Martha Li, Peter J. Ansell, Shun Lu
Journal: Journal of Clinical Oncology (2023)

9032 Background: The antibody-drug conjugate telisotuzumab vedotin (Teliso-V) is composed of the c-Met–targeting antibody telisotuzumab (ABT-700) linked to the microtubule inhibitor monomethyl auristatin E. In the LUMINOSITY study (NCT03539536), efficacy of Teliso-V was seen in patients (pts) with EGFR wildtype nonsquamous NSCLC and c-Met overexpression (≥25% tumor cells at 3+ intensity by IHC); overall response rate: 36.5%. Data are limited on whether specific driver oncogene states affect responses. We investigated genomic alterations in relation to response to Teliso-V in this population. Methods: Pts received 1.9 mg/kg Teliso-V monotherapy once every 2 weeks in LUMINOSITY. ctDNA was isolated from plasma collected at different timepoints. The PGDx elio plasma complete assay was used to identify genomic alterations in ctDNA samples. This assay included 521 genes for single nucleotide variants and insertion-deletion mutations, 38 for amplifications (amp), and 21 for translocations. Results: In total, 52 pts were included in the study; ctDNA from 48 pts was analyzed. The overall response rate among pts with ctDNA results was 37.5% (18 pts with partial response) compared with 36.5% for the ITT population of 52 pts. Genomic alterations are listed in the Table.Three out of 4 pts with MET amp at baseline responded, accounting for 17% of total responses. The observed MET amp frequency in this MET IHC preselected cohort was 8%, which is similar to the prevalence observed in tissue analysis by FISH. Of note, 1 nonresponder harbored a MET ex14del mutation at baseline, and a responder had a low-frequency mutation detected at the final visit. Mutations in KRAS were the most common genomic alteration and were detected in 13 (27%) pts at baseline. Three pts with a KRAS mutation were responders; among these, 2 out of 3 had a KRAS G12C mutation (seen in 3 pts total). Response rates were higher in pts with MET amp (75%; 95% CI: 0.30, 0.95) vs those without MET amp (34%; 0.22, 0.49), and higher in pts without KRAS mutations (43%; 0.28, 0.59) vs those with KRAS mutations (23%; 0.08, 0.50); however, confidence intervals were wide and larger sample sizes are needed. Conclusions: MET amp occurred more frequently in responders; however, Teliso-V activity was not restricted to these pts, as most responders were not MET amplified. Specific genomic alterations beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or did not respond to Teliso-V. Additional research on this topic is needed in larger pt cohorts and/or with tissue-based NGS analyses. [Table: see text]
A supervised remote exercising program for patients receiving immunotherapy alone or in combination with chemotherapy in Brazil: ExIO.
Authors: Paulo Gustavo Bergerot, Cristiane Decat Bergerot, Jonas Ribeiro Gomes Silva, Marcio Almeida Paes, Janice Farias, Dr. Paulo Sergio Lages, William Hiromi Fuzita, Igor Alexandre Protzner Morbeck, Daniel Sobreira de Oliveira Buso, Gabriel dos Anjos, Augusto Portieri Prata, Ana Carolina Salles de M. Ferreira, Marcos V S Franca, Carolina Bezerra Patriota, Camila Donini Tapia, Douglas Manfroi de Souza, Daniel Vargas Pivato de Almeida, Murilo Buso, Narjust Florez, Enrique Soto Pérez de Celis
Journal: Journal of Clinical Oncology (2023)

12122 Background: Exercise has been shown to ameliorate the side effects of cancer therapy, improve quality of life, and may even enhance treatment response. Since immunotherapy is widely used and approved for over 18 indications, studies are needed to determine the effect of exercise on immunotherapy outcomes Additionally, there is a crucial need for understanding how to make such interventions cost-effective and accessible in low- and middle-income countries. We aimed to explore the feasibility and efficacy of a remote exercise program for patients receiving immunotherapy alone or in combination with chemotherapy in Brazil. Methods: This is a 12-week prospective study of a supervised remote exercise program. Patients diagnosed with any solid cancer receiving immunotherapy alone or in combination are eligible. The program is supervised using the WhatsApp and Vedius platforms and consists of resistance and aerobic exercises for 3 to 5 hours per week (4 to 6 days a week). Outcome measures include treatment-related symptoms (FACT-ICM, scale 0-100), fatigue (BFI, scale 0-90), and overall quality of life (FACT-G, scale 0-108). Descriptive statistics were generated, and RM-ANOVA were used to evaluate changes in outcome measures over time. Results: A total of 40 patients have been enrolled to date, with 87.8% of complete adherence. Participants had a mean age of 59 years (SD = 12.2) and were predominantly female (53.7%), white (68.3%), married (68.3%), and had a college degree or higher education (56.0%). Patients were mostly diagnosed with breast (24.4%) or kidney (22.0%) cancers; 63.4% of patients had stage IV disease. Notably, significant improvements in treatment-related symptoms (M 1 = 86.5, M 2 = 96.0, p = 0.001), fatigue (M 1 = 21.4, M 2 = 9.6, p = 0.001) and quality of life (M 1 = 87.5, M 2 = 98.6, p = 0.001) have been observed. Conclusions: To our knowledge, this is the first study to examine the feasibility and efficacy of a supervised remote exercise program among patients with cancer receiving immunotherapy in Latin America. Our findings suggest that this remote program has high adherence and may improve treatment-related symptoms, fatigue, and overall quality of life while providing a practical and easily accessible alternative to patients. This study will be validated in an upcoming randomized clinical trial.
Pirtobrutinib in covalent BTK-inhibitor (cBTKi) pre-treated mantle cell lymphoma (MCL): Updated results and subgroup analysis from the phase 1/2 BRUIN study with &gt;3 years follow-up from start of enrollment.
Authors: Nirav Niranjan Shah, Wojciech Jurczak, Pier Luigi Zinzani, Toby A. Eyre, Chan Cheah, Chaitra Shankar Ujjani, Koji Izutsu, Shuo Ma, Ian W. Flinn, Alvaro Jose Alencar, David John Lewis, Krish Patel, Kami J. Maddocks, Yucai Wang, Talha Munir, Andrew David Zelenetz, Minna Balbas, Donald E Tsai, Chunxiao Wang, Michael Wang
Journal: Journal of Clinical Oncology (2023)

7514 Background: Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi. Here, we report updated results of pirtobrutinib in patients (pts) with cBTKi pre-treated relapsed/refractory (R/R) MCL and more than 3 years follow-up from start of enrollment. Methods: Pts with cBTKi pre-treated R/R MCL received pirtobrutinib monotherapy in a multicenter phase 1/2 BRUIN trial (NCT03740529). Efficacy was assessed in the prespecified primary efficacy cohort that comprised the first 90 enrolled pts who had measurable disease, had received a prior cBTKi, and had no known central nervous system involvement. The primary endpoint was overall response rate (ORR) as assessed by independent review committee. Secondary endpoints included duration of response (DOR) and safety. A data cut of 29 July 2022 was utilized. Results: Among MCL pts who received a prior cBTKi (n=90), median age was 70 years (range, 46-87), median prior lines of therapy were 3 (range, 1-8), 82% discontinued a prior cBTKi due to disease progression, and 78% had intermediate/high risk sMIPI score. Of samples available, 17/36 (47%) had TP53 mutations and 25/34 (74%) had Ki67 ≥30%. The ORR was 57% (95% CI, 46-67), including 19% complete responses (n=17) and 38% partial responses (n=34). At a median follow-up time of 13 months, the median DOR among the 51 responding pts was 17.6 months (95% CI, 7.3-27.2). The 12- and 18-month estimated DOR rates were 58% (95% CI, 41-72) and 45% (95% CI, 27-61), respectively. ORR and DOR by subgroups are shown in the Table. The median progression-free survival was 7.4 months (95% CI, 5.3–13.3). The median overall survival was 23.5 months (95% CI, 15.9-NE). In the MCL safety cohort (n=166), the most frequent treatment-emergent adverse events (TEAE) were fatigue (31%), diarrhea (22%), and anemia (17%). The most common Grade ≥3 TEAE was neutropenia (15%). Grade ≥3 TEAE of hemorrhage (3%) and atrial fibrillation/flutter (2%) were infrequent. Only 5 (3%) pts discontinued due to a treatment-related AE. Conclusions: Pirtobrutinib continues to show durable efficacy and a favorable safety profile in heavily pre-treated R/R MCL pts with prior cBTKi therapy. Responses were observed in pts with high-risk disease features including pts with blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations. Clinical trial information: NCT03740529 . [Table: see text]
A contemporary national population-based analysis of demographics and outcomes of Hispanics with adult T-cell leukemia/lymphoma in the US.
Authors: Carolina Velez-Mejia, Ian Michael Mines, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque
Journal: Journal of Clinical Oncology (2023)

e18771 Background: Adult T-cell Leukemia/Lymphoma (ATL) is a malignancy caused by the human T-cell leukemia virus type I with heterogenous clinical course (Blood Adv PMID29545256 J Clin Exp Hematop PMID34937829). There are endemic regions, but emigration has increased its incidence in the United States (US) (Hematol Oncol Clin North AmPMID2834087). There is a need to recognize trends and ethnic patterns to better understand this malignancy (J Oncol Pract PMID28796966 Blood Adv PMID29545256). This is the first national population-based analysis evaluating ethnic differences for HI diagnosed with ATL in the US. Methods: Data were analyzed on ATL patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) database between 2000-2018. Demographic, clinical and survival patterns were analyzed. Kaplan-Meier and Cox regression analyses were used when appropriate. Multivariate analysis and propensity score matching were performed with adjustment for age, stage and B-symptoms. Results: 598 patients (HI=65, NH=533) were diagnosed with ATL. Male sex predominated in in both. HI were diagnosed at a younger median age, 52 years (y) vs 63y for NH [p&lt;0.001]. Most of HI presented in the age bracket of 40-60y, while NH were identified between 60-80y [p &lt;0.001]. Regarding race, most of HI and NH were whites 82% vs 52% respectively, however, for NH Blacks and Asian/Pacific Islander were noted to be representative in the sample [p &lt;0.001]. The majority of HI were diagnosed between 2010-2014, however for NH, same incidence was reported from 2005-2009 and 2010-2014 [p = 0.107]. For both group the presence of B symptoms was predominantly unknown. The median survival for HI was 1.5y vs 0.8y for NH. The survival probability at 2, 5 and 10y for HI corresponded to 0.474, 0.341 and 0.238, while for NH it was 0.347, 0.244 and 0.153, respectively. The OS probability at 10y had no statistically significant difference but a tendency favoring HI [p = 0.053]. On multivariate analysis, when adjusted for age, those patients who were older than 80y and between 60-80 y, had worse OS compared to those younger than 60y, with Hazard Ratio of 3.9 (95% CI: 2.7 – 5.6) and 1.7 (95% CI: 1.2 – 2.2), respectively. Conclusions: This national population-based study identified similar OS in HI diagnosed with ATL in the US. The median survival time was noted to be higher for HI and the OS had a tendency favoring this group; however, findings are not yet significant. This association should be further analyzed as there may be unique oncologic response in this ethnic minority. HI may have remarkable immunologic reaction to infection due to oncogenic viruses plus the creation of a distinct tumor microenvironment. Recognizing clinical trends and identifying genetic predictors may assist in constructing more accurate prognostic indices to deliver targeted therapy.
The power of writing: Impact of writing for health professionals working with oncology patients.
Authors: Sabrina Chagas, Ana Coradazzi, Ricardo Caponero
Journal: Journal of Clinical Oncology (2023)

e23002 Background: Healthcare professionals are subject to stressful events, especially in areas such as oncology or palliative care. Writing is a valuable tool for dealing with stress, increasing empathy and job satisfaction. Narratives have therapeutic potential and can provide useful information for diagnosis and individualized strategies. Expressive Writing and Narrative Medicine have been studied in this field, resulting in physical and psychological benefits to health professionals, and can be a medical-educational tool. The practice of writing can promote healthier relationships between patients, professionals, and oneself. However, little is known about the perception that health professionals have about writing as a habit. These data can help to develop strategies for stimulating practice in universities, contributing to better professionals mental health. Methods: An online questionnaire was disseminated through social networks of the authors and professional associations inviting health professionals who deal with cancer patients and have the habit of writing to answer the questions, voluntarily and anonymously. The questionnaire was composed by 13 multiple choice questions and 1 free choice question, divided into 3 categories: 3 related to personal and professional data, 5 to the habit of writing and 5 to the impact that the habit of writing has on their lives. The data were analyzed descriptively, based on the results provided by the platform itself. Results: 177 responses to the form were obtained. Most participants were over 40 years old (53.9%). Eighty-seven participants were physicians (49.4%), 41 psychologists (23.3%), and 27.3% worked in other health fields. The majority (32.1%) declared they write sporadically when they feel the need. Only 17.8% wrote daily. Thirty-two percent write mainly short texts (blogs or social networks); 16.9% write mainly narratives. Most participants have been writing for more than ten years (63.2%). Using writing as a tool for self-knowledge was the main reason to start writing for 19.8%, and improving the ability to understand what is happening to other people for 18.7%. The themes of the texts were personal experiences (21.1%), personal feelings (19.4%), technical issues (14.8%), the process of getting sick (6.2%), or other topics (28.5%). Most reported that writing provides them with serenity (24.4%), comfort (23.8%), pride (19.3%), relief (13.6%), or other. Participants reported that the impact of writing on their lives is essential (32%), very positive (30.9%), or positive (33.7%), and the majority (48.8%) reported that the impact is both immediate and long-term. Conclusions: The personal perception about the impact of writing is extremely positive among healthcare professionals, suggesting that the practice should be stimulated during professional training and considered as a useful tool for the promotion of mental health.
Real world prognostic utility of body mass index and platelet lymphocyte ratio in first-line immunotherapy response in stage IV non-small cell lung cancer.
Authors: Madeline MacDonald, Robert Hsu, Darin Poei, Alexis Leyba, Krithika Chennapan, Christopher Leon, Raymond Diep, Kush Gaur, Bing Xia, Jorge J. Nieva
Journal: Journal of Clinical Oncology (2023)

e21092 Background: Meta-analyses show that increasing body mass index (BMI) may be associated with improved overall survival (OS) and progression free survival (PFS) compared to those with lower BMIs in patients receiving immunotherapy (IO). Pretreatment elevated platelet lymphocyte ratio (PLR) has been attributed to inferior PFS and OS in patients receiving IO. Our study evaluated real world data of Stage IV Non-Small Cell Lung Cancer (NSCLC) patients receiving first line (1L) treatment regimens involving immunotherapy while evaluating prognostic utility of BMI and PLR. Methods: Of the patients treated at USC Norris Comprehensive Cancer Center and LAC+USC Medical Center from 2015-2022, we looked at 75 Stage IV patients without EGFR, ALK, ROS1 mutations who received 1L IO therapy. Primary outcomes included PFS and OS from time of IO with a particular interest for patients with pre-treatment BMI &lt; 22 and PLR &gt; 180. Patients with previous IO exposure were excluded. Kaplan-Meier analysis using log-rank test was performed to evaluate for OS. Multivariate Cox proportion hazards regression was used for multivariate analysis of OS. Results: The median age at start of IO was 67.5 years with 49 (65.3%) males. 24 (32.0%) had BMI &lt; 22. 40/70 (57.7%) had PLR &gt; 180 at the start of 1L IO. Adenocarcinoma was the most common histology 50 (66.7%). 22 (29.3%) had PD-L1 &gt; TPS 50% and 20 (26.7%) had PD-L1 TPS 1-49%. Pembrolizumab was the most common IO used 60/75 (80%) and 43/75 (57.3%) received chemotherapy with IO. Patients with a BMI &lt; 22 had an inferior OS (BMI &lt; 22: 13.1 vs. BMI &gt; 28: 37.4 months (mos), p-value = 0.0420) with a trend towards worse PFS (BMI &lt; 22: 6.2 mos vs. BMI &gt; 28: 16 mos, p = 0.1702). Patients with PLR &gt; 180 had an inferior PFS (4.4 vs. 11.1 mos, p-value = 0.025) and OS (8.3 vs. 23.0 mos, p-value = 0.0277). A composite of BMI &lt; 22 and PLR &gt; 180 had the worst OS (p-value = 0.0385) with a trend towards worse PFS (p-value = 0.1702). (Table 1) Multivariate analysis for OS controlling for age, smoking, gender, PD-L1 TPS, and histology showed that BMI (HR: 0.8739, 95% CI: 0.7966-0.9492) and PLR &gt; 180 (HR: 2.286, 95% CI: 1.102-4.916) were significant for higher mortality risk. Conclusions: Patients with a composite profile of BMI &lt; 22 and PLR &gt; 180 had a significantly worse OS. This highlights the importance for pre-treatment screening for low BMI and high PLR to help provide additional supportive care in these patients prior to IO therapy. [Table: see text]